| First Author | Wu L | Year | 2016 |
| Journal | Eur J Immunol | Volume | 46 |
| Issue | 3 | Pages | 582-92 |
| PubMed ID | 26660726 | Mgi Jnum | J:247258 |
| Mgi Id | MGI:5922930 | Doi | 10.1002/eji.201545924 |
| Citation | Wu L, et al. (2016) Pathogenic IL-23 signaling is required to initiate GM-CSF-driven autoimmune myocarditis in mice. Eur J Immunol 46(3):582-92 |
| abstractText | Using a mouse model of experimental autoimmune myocarditis (EAM), we showed for the first time that IL-23 stimulation of CD4(+) T cells is required only briefly at the initiation of GM-CFS-dependent cardiac autoimmunity. IL-23 signal, acting as a switch, turns on pathogenicity of CD4(+) T cells, and becomes dispensable once autoreactivity is established. Il23a(-/-) mice failed to mount an efficient Th17 response to immunization, and were protected from myocarditis. However, remarkably, transient IL-23 stimulation ex vivo fully restored pathogenicity in otherwise nonpathogenic CD4(+) T cells raised from Il23a(-/-) donors. Thus, IL-23 may no longer be necessary to uphold inflammation in established autoimmune diseases. In addition, we demonstrated that IL-23-induced GM-CSF mediates the pathogenicity of CD4(+) T cells in EAM. The neutralization of GM-CSF abrogated cardiac inflammation. However, sustained IL-23 signaling is required to maintain IL-17A production in CD4(+) T cells. Despite inducing inflammation in Il23a(-/-) recipients comparable to wild-type (WT), autoreactive CD4(+) T cells downregulated IL-17A production without persistent IL-23 signaling. This divergence on the controls of GM-CSF-dependent pathogenicity on one side and IL-17A production on the other side may contribute to the discrepant efficacies of anti-IL-23 therapy in different autoimmune diseases. |
